Total synthesis of dihydroclerodin from (R)-(-)-carvone

Article abstract of DOI:10.1021/jo991151r

The first total synthesis of the natural enantiomer of the insect- antifeedant dihydroclerodin (1) and lupulin C (40) has been achieved starting from (R)-(-)-carvone (2). In the applied strategy, the hexahydrofuro[2,3- b]furan moiety was introduced in an early stage of the synthesis: The correct configuration at C-9, C-11, C-13, and C-16 was established by application of a remarkably diastereoselective Mukaiyama reaction. The desired configuration at C-10 was obtained by catalytic reduction of the intermediate enone 21. After annulation of the second ring, the structural features at C-4, C-5, and C-6 were introduced. The successful finishing of the synthesis included a Chugaev elimination to give the exocyclic double bond at C-4 that is present in lupulin C. Oxidation of this double bond with m-CPBA afforded dihydroclerodin.